Equipment and processes are known for aseptic vacuum filling and stoppering of liquids into syringes. Current processes and equipment are capable of vacuum filling and stoppering viscous liquids without a significant gas bubble, however these processes are not suitable for vacuum filling and stoppering of low viscosity liquids with no appreciable gas bubble.
Gas bubbles located inside a syringe expand when the syringe is exposed to a change in gas pressure, such as that experienced at higher elevations. In such circumstances, a plunger will move up the barrel of the syringe until the external pressure is returned to its original level, at which point the plunger will return to its original position. This plunger movement may introduce micro-organisms or other contaminants into the product contained in the syringe. The amount of plunger movement is proportional to the size of the gas bubble inside the syringe and the difference in pressure between the pressure at which the syringe was filled and the ambient pressure to which the syringe is then exposed.
In current processes for vacuum stoppering or vacuum filling of containers with low viscosity liquids, sub optimal vacuum levels have to be applied or only a small percentage of the syringe can be filled (50% or less) due to splashing, out-gassing and boil over of the liquid in the syringe when under vacuum. Viscous liquids can be filled and stoppered under optimal deep vacuum as their viscosities inhibit liquid splashing, out-gassing and boiling. Another difficulty that arises in vacuum filling of low viscosity liquids is controlling fill volume. With low viscosity liquids, the liquid that is in the filling line between the needle outlet and the fill pump outlet is forced out of the line into the syringe by out-gassing of the liquid and expansion of gas bubbles under vacuum. This is not a concern in filling containers with viscous liquids.
Processes that can fill syringes without gas bubbles offer significant benefits to products that are air sensitive, shear sensitive and degraded by liquid gas interfaces (i.e. some proteins). Further, aseptic conditions in syringes in which the plunger (plunger) is free to move in response to external pressure changes are improved by bubble-free filling. There is a need for bubble-free filling that produces a filled container such as a syringe with no gas bubble and that reduces or eliminates plunger movement described above.